Mechanism linking NMDA receptor activation to modulation of voltage-gated sodium current in distal retina.
Mechanism linking NMDA receptor activation to modulation of voltage-gated sodium current in distal retina.
复制标题
将 NMDA 受体激活与远端视网膜电压门控钠电流调节联系起来的机制。
DOI：
10.1152/ajpcell.00256.2002
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发表时间：
2003
期刊：
影响因子：
--
通讯作者：
Linn,CindyL
中科院分区：
文献类型：
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作者：
Davis,ScottF;Linn,CindyL
在这项研究中，我们研究了分离的鲶鱼视锥水平细胞中N-甲基-D-天冬氨酸（NMDA）受体激活与电压门控钠通道抑制之间的联系机制。在低钙盐水中孵育或用钙螯合剂BAPTA透析的电压钳位细胞中激活NMDA通道，以确定钠通道调节所需的通过NMDA通道的钙内流。为了确定通过NMDA通道的钙内流是否触发钙诱导的钙释放（CICR），用钙敏感染料钙绿色2加载细胞，并测量响应于NMDA的相对荧光的变化。反应进行了比较，当咖啡因耗尽商店获得的测量。电压钳研究表明，CICR调节钠通道的方式类似于NMDA。用AP-7阻断NMDA受体，用钌红阻断CICR，用咖啡因消耗储存，或用钙调蛋白拮抗剂W-5或肽290-309透析细胞都可以阻止钠通道调节。这些结果支持的假设，NMDA调制的电压门控钠通道在水平的细胞需要CICR和激活的钙调素依赖性信号通路。
In this study, we investigated the mechanism that links activation ofN-methyl-D-aspartate (NMDA) receptors to inhibition of voltage-gated sodium channels in isolated catfish cone horizontal cells. NMDA channels were activated in voltage-clamped cells incubated in low-calcium saline or dialyzed with the calcium chelator BAPTA to determine that calcium influx through NMDA channels is required for sodium channel modulation. To determine whether calcium influx through NMDA channels triggers calcium-induced calcium release (CICR), cells were loaded with the calcium-sensitive dye calcium green 2 and changes in relative fluorescence were measured in response to NMDA. Responses were compared with measurements obtained when caffeine depleted stores. Voltage-clamp studies demonstrated that CICR modulated sodium channels in a manner similar to that of NMDA. Blocking NMDA receptors with AP-7, blocking CICR with ruthenium red, depleting stores with caffeine, or dialyzing cells with calmodulin antagonists W-5 or peptide 290–309 all prevented sodium channel modulation. These results support the hypothesis that NMDA modulation of voltage-gated sodium channels in horizontal cells requires CICR and activation of a calmodulin-dependent signaling pathway.